title: The immune response elicited by mammary adenocarcinoma cells transduced with interferon-gamma and cytosine deaminase genes cures lung metastases by parental cells.
abstract: The parental cells of the TSA murine mammary adenocarcinoma (TSA-pc) were transfected with both the interferon-gamma (IFN-y) gene and the cytosine deaminase (CD) suicide gene to obtain a therapeutic vaccine active against TSA-pc lung metastases. Even in the absence of treatment with the prodrug 5-fluorocytosine (5-FC), the local growth of double transfectants (CD-y clones) was inhibited by a marked recruitment of granulocytes and macrophages. In mice harboring TSA-pc micrometastases, therapeutic vaccination with either IFN-gamma or CD single transfectants reduced the number of lung nodules, whereas CD-gamma double transfectants abrogated metastasis growth in up to 80% of mice. Treatment of mice with 5-FC did not alter the curative efficacy of CD-gamma double-transfectant cells. By contrast, in mice vaccinated with CD single-transfectant cells, 5-FC treatment caused a significant loss of their curative activity. Host T cells played an active role in the cure of lung metastases, because vaccination of nude mice with CD-gamma cells was uneffective.
authors.affiliation: Institute for Cancer Research and Centro Interdipartimentale di Ricerche sul Cancro G. Prodi, University of Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Nanni
authors.forename: C
authors.initials: C
authors.lastname: De Giovanni
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
authors.forename: L
authors.initials: L
authors.lastname: Landuzzi
authors.forename: I
authors.initials: I
authors.lastname: Rossi
authors.forename: F
authors.initials: F
authors.lastname: Frabetti
authors.forename: M
authors.initials: M
authors.lastname: Giovarelli
authors.forename: G
authors.initials: G
authors.lastname: Forni
authors.forename: F
authors.initials: F
authors.lastname: Cavallo
authors.forename: E
authors.initials: E
authors.lastname: Di Carlo
authors.forename: P
authors.initials: P
authors.lastname: Musiani
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D043525:Cytosine Deaminase; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D007371:Interferon-gamma; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase